Loss of lung mitochondrial aconitase activity due to hyperoxia in bronchopulmonary dysplasia in primates.
The premature primate exposed to hyperoxia provides a useful model of bronchopulmonary dysplasia. A critical target in hyperoxic injury is the mitochondrial matrix enzyme aconitase. We hypothesized that this enzyme's activity would decline in the premature baboon lung during exposure to hyperoxia. Total aconitase activity was significantly decreased in the lungs of premature baboons of 140 days gestation with exposure to 100% oxygen for 6-10 days compared with as needed [pro re nada (PRN)] oxygen exposure and fetal controls (P = 0.0001). In activity gels, lungs from 100% oxygen-exposed animals (6-10 days) showed a nearly complete loss of mitochondrial aconitase activity relative to lungs from animals exposed only to PRN oxygen. Decreased lung aconitase activity was not a nonspecific effect of hyperoxia, causing mitochondrial damage or loss, because the activity of the mitochondrial respiratory enzyme cytochrome oxidase was not different in lungs of 100% oxygen-exposed relative to PRN oxygen-exposed newborns. In 125-day-gestation premature primates (age 6-10 days), lung total aconitase activity was correlated with inspired oxygen tension (r = 0.73 for fraction of inspired oxygen > 0.35), whereas, for animals of 140 days gestation, no such correlation was found. Thus the more premature animal's lung was more susceptible to loss of aconitase.
Morton
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RL
National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver 80206, USA.
Iklé
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D
White
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CW
D000154:Aconitate Hydratase / Q000378:metabolism*; D000818:Animals; D001997:Bronchopulmonary Dysplasia / Q000201:enzymology / Q000503:physiopathology*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005333:Fetus; D005865:Gestational Age; D006801:Humans; D018496:Hyperoxia; D007231:Infant, Newborn; D008168:Lung / Q000196:embryology* / Q000201:enzymology / Q000503:physiopathology*; D008928:Mitochondria / Q000201:enzymology*; D010215:Papio
D003576:Electron Transport Complex IV; D000154:Aconitate Hydratase